Field of Endeavor
A device, system and method for treatment of an opening in vascular and/or septal walls including patent foramen ovale.
State of Technology
Patent Foramen Ovale
Patent Foramen Ovale (“PFO”) is a genetic condition in which a remnant fetal opening in the septal wall causes shunting of unfiltered blood to the systemic circulation. This opening serves an important physiologic function during fetal development when blood is oxygenated by the mother, and after birth it typically closes due to the increased pressures in the heart. However, it is reported that in nearly 27% of the population it remains as an opening with a flap-like structure, and therefore, has the potential for allowing blood to pass directly from the right side of the heart to the left side of the heart. When this occurs, the blood bypasses the pulmonary system and clots present in the blood are not filtered out. These clots then pass directly to the systemic system, where they can lead to stroke. Of the cases of cryptogenic stroke, constituting 40% of all stroke cases, the occurrence rate of PFO is about 50-54%, as compared to 10-15% in control patients. Thus, PFO has been found to be involved in 20-22% of all stroke incidences. Incidences of stroke in such cases have been found to have a direct correlation with size of the septal opening and the degree of shunting caused, based on patient's physical activity. PFO has also been shown to be associated with other severe conditions like myocardial infarction, peripheral embolism, decompression illness, migraines and hypoxaemia to name a few.
Current Treatment of PFO
Present treatments for PFO include medical therapy, such as anticoagulants, surgical repair, and transcatheter insertion of a device for sealing the opening. For the closure, percutaneous procedure is preferred over surgical repair and devices available on the market for this procedure include Amplatzer, PFO-Star, Clamshell Septal Umbrella, CardioSEAL septal occluder, and buttoned devices, among others. These devices sandwich the septal wall or occlude the opening in order to prevent leakage between the atria and to create a seal. Significant difference in performance among these devices has been reported with Amplatzer, designed with Nitinol based shape memory alloy frame that is filled with biodegradable polyester material, being the most commonly used. Residual shunting is common even after the transcathetral procedure and is found in about 50% subjects immediately after closure, and in about 40% subjects one month after closure.
Other Septal Defects
PFOs are a variation of atrial septal defects (ASDs) known as ostium secundum, which describes septal defects located near the center of the septum. Other common forms of ASD are ostium primum, which occur near in the lower part of the septum and are accompanied by an associated cleft in the mitral valve resulting in mitral regurgitation, and sinus venosus that are often accompanied by an anomalous pulmonary venous connection. Ostium primum and sinus venosus typically require surgical repair. Ventricular septal defects (VSD) are actually the most common form of congenital heart defect, and may be treated with transcatheter delivered septal occlusion devices. As with ASD, many different classifications of VSD describe the form, location, and hemodynamic implications. While VSD closure via transcatheter therapy is considered more challenging due to variations in position, form and location, two types of VSD have emerged as favorable candidates for transcatheter closure: muscular and perimembranous VSDs. Also, more recently, VSDs resulting from septal rupture induced by myocardial infarction have been targeted for transcatheter device closure. Presently, devices very similar to those used to treat PFO and ASD are employed to treat VSD in qualified candidates, i.e. the concept is the same, and however the geometry of the device varies. Ostium secundum ASDs, and muscular and perimembranous VSDs can potentially be treated by the device of this invention.
Shape Memory Polymers (SMPs)
Thermally actuated shape memory polymers (SMPs) have the ability to transform from a stable “secondary” shape to a predetermined “primary” shape when heated or otherwise activated. This ability stems from the polymer morphology, which is generally described as consisting of a shape-fixing matrix phase (amorphous or semi-crystalline polymer) and a shape memorizing dispersed phase (physical or chemical crosslinks). The “primary” shape is typically programmed into the material during its original melt processing or curing process. The temporary “secondary” shape is obtained by deforming the material while heating it above the characteristic thermal transition temperature, Tt, and then cooling to fix the shape. Tt can be either the glass transition Tg, or melting, Tm, temperature depending on the polymer system. A detailed description of the fundamental principles of shape memory behavior is given by Lendlein and Kelch (Lendlein, A. and S. Kelch, Shape-memory polymers. Angew Chem Int Ed, 2002. 41: p. 2034-2057).
A number of SMP-based medical devices have been proposed. A recent review of thermally actuated SMPs in medicine can be found in Small, W., P. Singhal, T. S. Wilson, and D. J. Maitland, Biomedical applications of thermally activated shape memory polymers. Journal of Materials Chemistry, 2010. 20 (17): p. 3356-3366. SMP biomedical applications include thrombectomy devices to treat ischemic stroke, embolic coils to fill aneurysms, and vascular stents. Encouraging biocompatibility data (Cabanlit, M., D. J. Maitland, T. S. Wilson, S. Simon, T. Wun, M. E. Gershwin, and J. Van de Water, Polyurethane shape-memory polymers demonstrate functional biocompatibility in vitro Macromol Biosci 2007. 7: p. 48-55) and the recent, first SMP, approval by the FDA of a shoulder anchor device (Melkerson, M. N. Food and Drug Administration 510(k) approval of Medshape Solution's SMP shoulder anchor. 2009; Available from the website of the Food and Drug Administration (www.fda.gov/cdrh/pdf8/K083792.pdf) have been reported for SMP materials.
Biodegradable SMPs
The importance of biodegradability of polymeric materials has long been acknowledged, and several comprehensive reviews have been published on them as early as 1990s (See Albertsson, A. and S. Karlsson, Chemistry and Biochemistry of Polymer degradation, in Chemistry and technology of biodegradable polymers, G. J. L. Griffin, Editor. 1994, Blackie Academic & Professional, an imprint of Chapman & Hall: Glasgow, UK. p. 48 and Amass, W., A. Amass, and B. Tighe, A review of biodegradable polymers: uses, current developments in the synthesis and characterization of biodegradable polyesters, blends of biodegradable polymers and recent advances in biodegradation studies. Polymer International, 1998. 47 (2): p. 89-144). Timeframes for the biodegradation of the most popular polymers have been compared by Holland et. al. (Holland, S. J., Novel polymeric controlled release systems. 1986, Aston University: Birmingham). Also the effect of the media pH has been studied and it has been shown that increase in hydrophilicity increases the rate of degradation of materials. Biodegradable materials have been shown to have very different degradation timeframes in-vitro and in-vivo due to the enzymatic factors and in vivo physiological conditions (abiotic vs. biotic degradation). When the mechanism of degradation is primarily hydrolytic cleavage of bonds, in-vitro and in-vivo results are shown to have better agreement.
Some known biodegradable polymers include polycaprolactonediols (PCL) that were either reacted with acrylic monomers and photocured to get a SMP network, or reacted with a diisocyanate to make a polyurethane. Biodegradability and shape memory behavior of 4,4-(adipoyldioxy)dicinnamic acid and poly(ethylene glycol) has also been studied. PCL based polymers typically show lower degradation rate, lower shape recovery and low mechanical strengths. In another series of investigations PLA based polyurethanes were developed and mechanical and shape memory properties were investigated for them. These showed better shape recovery but much higher actuation temperatures. Subsequently multiple copolymers based on PLA and PCL were reported to adjust shape memory behavior, biodegradability and actuation temperature to a desirable range. Other known biodegradable SMPs include amorphous copolyester urethane networks, poly(3-hydroxybutyrate)-co-(3-hydroxy valerate).
SMP Foams
The unique actuating properties of SMPs can be enhanced further through their structuring into low-density open cell foams. For example, a model isotropic SMP open cell foam should have an initial modulus that scales as the square of the solid volume fraction (φs) and a yield stress which scales with volume fraction to the 3/2 power. SMP foam with a solid volume fraction of 0.01 would be expected to have a modulus 0.0001 times that of neat SMP, with proportional decreases in recovery stress during actuation. Likewise, structuring SMP into foams significantly increases the range of strains (particularly volume changes) accessible to SMP devices, which can now be compressed into a very compact temporary form and thermally actuated to expand back to its original form.
It has been demonstrated that SMP foams with densities as low as 0.005 g/cc, corresponding to volume expansions in excess of a 100 times from a fully compressed shape can be made. While foams made using the process of pore templating via salt leaching are now common to tissue engineering applications, the resulting foams have relatively poor mechanical properties as compared to foams made by blowing methods. At the same time chemical and physical blowing processes are rare for materials with highly crosslinked molecular structures.